Chronic renal failure
Encyclopedia
Chronic kidney disease also known as chronic renal disease, is a progressive loss in renal function
over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell
and experiencing a reduced appetite
. Often, chronic kidney disease is diagnosed as a result of screening
of people known to be at risk of kidney problems, such as those with high blood pressure
or diabetes
and those with a blood relative with chronic kidney disease. Chronic kidney disease may also be identified when it leads to one of its recognized complications, such as cardiovascular disease
, anemia
or pericarditis
.
Chronic kidney disease is identified by a blood test
for creatinine
. Higher levels of creatinine indicate a falling glomerular filtration rate and as a result a decreased capability of the kidneys to excrete waste products. Creatinine levels may be normal in the early stages of CKD, and the condition is discovered if urinalysis
(testing of a urine sample) shows that the kidney is allowing the loss of protein
or red blood cell
s into the urine. To fully investigate the underlying cause of kidney damage, various forms of medical imaging
, blood tests and often renal biopsy
(removing a small sample of kidney tissue) are employed to find out if there is a reversible cause for the kidney malfunction. Recent professional guidelines classify the severity of chronic kidney disease in five stages, with stage 1 being the mildest and usually causing few symptoms and stage 5 being a severe illness with poor life expectancy if untreated. Stage 5 CKD is also called established chronic kidney disease and is synonymous with the now outdated terms end-stage renal disease (ESRD), chronic kidney failure (CKF) or chronic renal failure (CRF).
There is no specific treatment unequivocally shown to slow the worsening of chronic kidney disease. If there is an underlying cause to CKD, such as vasculitis
, this may be treated directly with treatments aimed to slow the damage. In more advanced stages, treatments may be required for anemia and bone disease
. Severe CKD requires one of the forms of renal replacement therapy
; this may be a form of dialysis
, but ideally constitutes a kidney transplant
.
or protein in the urine. As the kidney
function decreases:
People with chronic kidney disease suffer from accelerated atherosclerosis
and are more likely to develop cardiovascular disease
than the general population. Patients afflicted with chronic kidney disease and cardiovascular disease tend to have significantly worse prognoses than those suffering only from the latter.
, hypertension
, and glomerulonephritis
. Together, these cause approximately 75% of all adult cases. Certain geographic areas have a high incidence of HIV nephropathy.
Historically, kidney disease has been classified according to the part of the renal anatomy that is involved, to wit:
It is important to differentiate CKD from acute renal failure
(ARF) because ARF can be reversible. Abdominal ultrasound
, in which the size of the kidney
s is measured, is commonly performed. Kidneys with CKD are usually smaller (< 9 cm) than normal kidneys, with notable exceptions such as in diabetic nephropathy
and polycystic kidney disease
. Another diagnostic clue that helps differentiate CKD from ARF is a gradual rise in serum creatinine (over several months or years) as opposed to a sudden increase in the serum creatinine (several days to weeks). If these levels are unavailable (because the patient has been well and has had no blood tests), it is occasionally necessary to treat a patient briefly as having ARF until it has been established that the renal impairment is irreversible.
Additional tests may include nuclear medicine
MAG3 scan to confirm blood flows and establish the differential function between the two kidneys. DMSA
scans are also used in renal imaging; with both MAG3 and DMSA being used chelated
with the radioactive element Technetium-99
.
In chronic renal failure treated with standard dialysis, numerous uremic toxins accumulate. These toxins show various cytotoxic activities in the serum, have different molecular weights and some of them are bound to other proteins, primarily to albumin. Such toxic protein bound substances are receiving the attention of scientists who are interested in improving the standard chronic dialysis procedures used today.
All individuals with kidney damage are classified as having chronic kidney disease, irrespective of the level of GFR. The rationale for including individuals with GFR > 60 mL/min/1.73 m2 is that GFR may be sustained at normal or increased levels despite substantial kidney damage and that patients with kidney damage are at increased risk of the two major outcomes of chronic kidney disease: loss of kidney function and development of cardiovascular disease.
The loss of protein in the urine
is regarded as an independent marker for worsening of renal function and cardiovascular disease. Hence, British guidelines append the letter "P" to the stage of chronic kidney disease if there is significant protein loss.
Stage 1
Slightly diminished function; kidney damage with normal or relatively high GFR (≥90 mL/min/1.73 m2). Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies.
Stage 2
Mild reduction in GFR (60–89 mL/min/1.73 m2) with kidney damage. Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies.
Stage 3
Moderate reduction in GFR (30–59 mL/min/1.73 m2). British guidelines distinguish between stage 3A (GFR 45–59) and stage 3B (GFR 30–44) for purposes of screening and referral.
Stage 4
Severe reduction in GFR (15–29 mL/min/1.73 m2)
Preparation for renal replacement therapy
Stage 5
Established kidney failure (GFR <15 mL/min/1.73 m2, or permanent renal replacement therapy (RRT)
, also abbreviated as NDD-CKD, is a designation used to encompass the status of those persons with an established CKD
who do not yet require the life-supporting treatments for renal failure
known as renal replacement therapy
(including maintenance dialysis
or renal transplantation). The condition of individuals with CKD
, who require either of the 2 types of renal replacement therapy
(dialysis
or transplantation), is referred to as the end-stage renal disease (ESRD). Hence, the start of the ESRD is practically the irreversible
conclusion of the NDD-CKD. Even though the non-dialysis dependent status refers to the status of persons with earlier stages of CKD
(stages 1 to 4), patients with advanced stage of CKD
(Stage 5), who have not yet started renal replacement therapy
are also referred to as NDD-CKD.
and treatment of the original disease, whenever feasible, are the broad principles of management. Generally, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are used, as they have been found to slow the progression of CKD to stage 5. Although the use of ACE inhibitors and ARBs represents the current standard of care for patients with CKD, patients progressively lose kidney function while on these medications, as seen in the IDNT and RENAAL studies, which reported a decrease over time in estimated glomerular filtration rate (an accurate measure of CKD progression, as detailed in the K/DOQI guidelines) in patients treated by these conventional methods.
Currently, several compounds are in development for CKD. These include, but are not limited to, bardoxolone methyl
, olmesartan medoxomil, sulodexide
, and avosentan.
Replacement of erythropoietin
and calcitriol
, two hormones processed by the kidney, is often necessary in patients with advanced CKD. Phosphate binders
are also used to control the serum phosphate
levels, which are usually elevated in advanced chronic kidney disease.
When one reaches stage 5 CKD, renal replacement therapy
is required, in the form of either dialysis
or a transplant.
The normalization of hemoglobin has not been found to be of any benefit.
People with CKD are at a markedly increased risk of cardiovascular disease, and often have other risk factors for heart disease, such as hyperlipidemia
. The most common cause of death in people with CKD is therefore cardiovascular disease rather than renal failure. Aggressive treatment of hyperlipidemia is warranted.
has shown that all cause mortality
(the overall death rate) increases as kidney function decreases. The leading cause of death in patients with chronic kidney disease is cardiovascular disease, regardless of whether there is progression to stage 5.
While renal replacement therapies
can maintain patients indefinitely and prolong life, the quality of life
is severely affected. Renal transplantation increases the survival of patients with stage 5 CKD significantly when compared to other therapeutic options; however, it is associated with an increased short-term mortality (due to complications of the surgery). Transplantation aside, high intensity home hemodialysis
appears to be associated with improved survival and a greater quality of life
, when compared to the conventional three times a week hemodialysis
and peritoneal dialysis
.
In the US, the Centers for Disease Control and Prevention
found that CKD affected an estimated 16.8% of adults aged 20 years and older, during 1999 to 2004.
UK estimates suggest that 8.8% of the population of Great Britain and Northern Ireland have symptomatic CKD.
Chronic kidney disease (CKD) is a major concern in African Americans, mostly due to increased prevalence of hypertension. As an example, 37% of end-stage renal disease cases in African Americans can be attributed to high blood pressure, compared with 19% among caucasians. Treatment efficacy also differs between racial groups. Administration of anti-hypertensive drugs generally halts disease progression in white populations, but has little effect in slowing renal disease among blacks, and additional treatment such as bicarbonate therapy is often required. While lower socioeconomic status contributes to prevalence of CKD, there are still significant differences in CKD prevalence between African Americans and whites when controlling for environmental factors.
Studies have shown that there is a true association between history of chronic renal failure in first or second-degree relatives, and risk of disease. In addition, African Americans may have higher serum levels of human leukocyte antigens (HLA). High HLA concentrations can contribute to increased systemic inflammation, which indirectly may lead to heightened susceptibility for developing kidney disease. Lack of nocturnal reduction in blood pressure among groups of African Americans is also offered as an explanation, which lends further credence to a genetic etiology of CKD racial disparities.
is a national organization representing patients and professionals who treat kidney diseases. The American Kidney Fund
(AKF) is a national non-profit organization providing treatment-related financial assistance to 1 out of every 5 dialysis patients each year. The Renal Support Network
(RSN) is a nonprofit, patient-focused, patient-run organization that provides non-medical services to those affected by CKD. The American Association of Kidney Patients (AAKP) is a non-profit, patient-centric group focused on improving the health and well-being of CKD and dialysis
patients. The Renal Physicians Association
(RPA) is an association representing nephrology
professionals.
In the United Kingdom, the UK National Kidney Federation
represents patients, and the Renal Association
represents renal physicians and works closely with the National Service Framework
for kidney disease.
Kidney Health Australia serves that country.
The International Society of Nephrology
is an international body representing specialists in kidney diseases.
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
over a period of months or years. The symptoms of worsening kidney function are unspecific, and might include feeling generally unwell
Malaise
Malaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
and experiencing a reduced appetite
Anorexia (symptom)
Anorexia is the decreased sensation of appetite...
. Often, chronic kidney disease is diagnosed as a result of screening
Screening (medicine)
Screening, in medicine, is a strategy used in a population to detect a disease in individuals without signs or symptoms of that disease. Unlike what generally happens in medicine, screening tests are performed on persons without any clinical sign of disease....
of people known to be at risk of kidney problems, such as those with high blood pressure
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
or diabetes
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
and those with a blood relative with chronic kidney disease. Chronic kidney disease may also be identified when it leads to one of its recognized complications, such as cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
, anemia
Anemia
Anemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
or pericarditis
Pericarditis
Pericarditis is an inflammation of the pericardium . A characteristic chest pain is often present.The causes of pericarditis are varied, including viral infections of the pericardium, idiopathic causes, uremic pericarditis, bacterial infections of the precardium Pericarditis is an inflammation of...
.
Chronic kidney disease is identified by a blood test
Blood test
A blood test is a laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a needle, or via fingerprick....
for creatinine
Creatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
. Higher levels of creatinine indicate a falling glomerular filtration rate and as a result a decreased capability of the kidneys to excrete waste products. Creatinine levels may be normal in the early stages of CKD, and the condition is discovered if urinalysis
Urinalysis
A urinalysis , also known as Routine and Microscopy , is an array of tests performed on urine, and one of the most common methods of medical diagnosis...
(testing of a urine sample) shows that the kidney is allowing the loss of protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
or red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s into the urine. To fully investigate the underlying cause of kidney damage, various forms of medical imaging
Medical imaging
Medical imaging is the technique and process used to create images of the human body for clinical purposes or medical science...
, blood tests and often renal biopsy
Biopsy
A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...
(removing a small sample of kidney tissue) are employed to find out if there is a reversible cause for the kidney malfunction. Recent professional guidelines classify the severity of chronic kidney disease in five stages, with stage 1 being the mildest and usually causing few symptoms and stage 5 being a severe illness with poor life expectancy if untreated. Stage 5 CKD is also called established chronic kidney disease and is synonymous with the now outdated terms end-stage renal disease (ESRD), chronic kidney failure (CKF) or chronic renal failure (CRF).
There is no specific treatment unequivocally shown to slow the worsening of chronic kidney disease. If there is an underlying cause to CKD, such as vasculitis
Vasculitis
Vasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis...
, this may be treated directly with treatments aimed to slow the damage. In more advanced stages, treatments may be required for anemia and bone disease
Renal osteodystrophy
Renal osteodystrophy or chronic kidney disease-mineral and bone disorder is a bone pathology, characterized by bone mineralization deficiency, that is a direct result of the electrolyte and endocrine derangements that accompany chronic kidney disease...
. Severe CKD requires one of the forms of renal replacement therapy
Renal replacement therapy
Renal replacement therapy is a term used to encompass life-supporting treatments for renal failure.It includes:*hemodialysis,*peritoneal dialysis,*hemofiltration and*renal transplantation.These treatments will not cure chronic kidney disease...
; this may be a form of dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
, but ideally constitutes a kidney transplant
Kidney transplantation
Kidney transplantation or renal transplantation is the organ transplant of a kidney into a patient with end-stage renal disease. Kidney transplantation is typically classified as deceased-donor or living-donor transplantation depending on the source of the donor organ...
.
Signs and symptoms
CKD is initially without specific symptoms and can only be detected as an increase in serum creatinineCreatinine
Creatinine is a break-down product of creatine phosphate in muscle, and is usually produced at a fairly constant rate by the body...
or protein in the urine. As the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
function decreases:
- Blood pressureBlood pressureBlood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
is increased due to fluid overload and production of vasoactive hormones created by the kidney via the RAS (renin-angiotensin systemRenin-angiotensin systemThe renin-angiotensin system or the renin-angiotensin-aldosterone system is a hormone system that regulates blood pressure and water balance....
), increasing one's risk of developing hypertensionHypertensionHypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
and/or suffering from congestive heart failureCongestive heart failureHeart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition... - UreaUreaUrea or carbamide is an organic compound with the chemical formula CO2. The molecule has two —NH2 groups joined by a carbonyl functional group....
accumulates, leading to azotemiaAzotemiaAzotemia is a medical condition characterized by abnormally high levels of nitrogen-containing compounds, such as urea, creatinine, various body waste compounds, and other nitrogen-rich compounds in the blood...
and ultimately uremiaUremiaUremia or uraemia is a term used to loosely describe the illness accompanying kidney failure , in particular the nitrogenous waste products associated with the failure of this organ....
(symptoms ranging from lethargy to pericarditisPericarditisPericarditis is an inflammation of the pericardium . A characteristic chest pain is often present.The causes of pericarditis are varied, including viral infections of the pericardium, idiopathic causes, uremic pericarditis, bacterial infections of the precardium Pericarditis is an inflammation of...
and encephalopathyEncephalopathyEncephalopathy means disorder or disease of the brain. In modern usage, encephalopathy does not refer to a single disease, but rather to a syndrome of global brain dysfunction; this syndrome can be caused by many different illnesses.-Terminology:...
). Urea is excreted by sweating and crystallizes on skin ("uremic frost"). - PotassiumPotassiumPotassium is the chemical element with the symbol K and atomic number 19. Elemental potassium is a soft silvery-white alkali metal that oxidizes rapidly in air and is very reactive with water, generating sufficient heat to ignite the hydrogen emitted in the reaction.Potassium and sodium are...
accumulates in the blood (known as hyperkalemiaHyperkalemiaHyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
with a range of symptoms including malaiseMalaiseMalaise is a feeling of general discomfort or uneasiness, of being "out of sorts", often the first indication of an infection or other disease. Malaise is often defined in medicinal research as a "general feeling of being unwell"...
and potentially fatal cardiac arrhythmias) - ErythropoietinErythropoietinErythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
synthesis is decreased (potentially leading to anemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
, which causes fatigueFatigue (physical)Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...
) - Fluid volume overloadFluid balanceFluid balance is the concept of human homeostasis that the amount of fluid lost from the body is equal to the amount of fluid taken in. Euvolemia is the state of normal body fluid volume. Water is necessary for all life on Earth...
— symptoms may range from mild edemaEdemaEdema or oedema ; both words from the Greek , oídēma "swelling"), formerly known as dropsy or hydropsy, is an abnormal accumulation of fluid beneath the skin or in one or more cavities of the body that produces swelling...
to life-threatening pulmonary edemaPulmonary edemaPulmonary edema , or oedema , is fluid accumulation in the air spaces and parenchyma of the lungs. It leads to impaired gas exchange and may cause respiratory failure... - HyperphosphatemiaHyperphosphatemiaHyperphosphatemia is an electrolyte disturbance in which there is an abnormally elevated level of phosphate in the blood. Often, calcium levels are lowered due to precipitation of phosphate with the calcium in tissues.-Signs and symptoms:...
— due to reduced phosphate excretion, associated with hypocalcemia (due to 1,25 dihydroxyvitamin D3 deficiency). The 1,25 dihydroxyvitamin D3 deficiency is due to stimulation of fibroblast growth factor-23.- Later this progresses to secondary hyperparathyroidismSecondary hyperparathyroidismSecondary hyperparathyroidism refers to the excessive secretion of parathyroid hormone by the parathyroid glands in response to hypocalcemia and associated hypertrophy of the glands. This disorder is especially seen in patients with chronic renal failure...
, renal osteodystrophyRenal osteodystrophyRenal osteodystrophy or chronic kidney disease-mineral and bone disorder is a bone pathology, characterized by bone mineralization deficiency, that is a direct result of the electrolyte and endocrine derangements that accompany chronic kidney disease...
and vascular calcification that further impairs cardiac function.
- Later this progresses to secondary hyperparathyroidism
- Metabolic acidosisMetabolic acidosisIn medicine, metabolic acidosis is a condition that occurs when the body produces too much acid or when the kidneys are not removing enough acid from the body. If unchecked, metabolic acidosis leads to acidemia, i.e., blood pH is low due to increased production of hydrogen by the body or the...
, due to accumulation of sulfates, phosphates, uric acid etc. This may cause altered enzyme activity by excess acid acting on enzymes and also increased excitability of cardiac and neuronal membranes by the promotion of hyperkalemiaHyperkalemiaHyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
due to excess acid (acidemia)
People with chronic kidney disease suffer from accelerated atherosclerosis
Atherosclerosis
Atherosclerosis is a condition in which an artery wall thickens as a result of the accumulation of fatty materials such as cholesterol...
and are more likely to develop cardiovascular disease
Cardiovascular disease
Heart disease or cardiovascular disease are the class of diseases that involve the heart or blood vessels . While the term technically refers to any disease that affects the cardiovascular system , it is usually used to refer to those related to atherosclerosis...
than the general population. Patients afflicted with chronic kidney disease and cardiovascular disease tend to have significantly worse prognoses than those suffering only from the latter.
Causes
The most common causes of CKD are diabetes mellitusDiabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
, hypertension
Hypertension
Hypertension or high blood pressure is a cardiac chronic medical condition in which the systemic arterial blood pressure is elevated. What that means is that the heart is having to work harder than it should to pump the blood around the body. Blood pressure involves two measurements, systolic and...
, and glomerulonephritis
Glomerulonephritis
Glomerulonephritis, also known as glomerular nephritis, abbreviated GN, is a renal disease characterized by inflammation of the glomeruli, or small blood vessels in the kidneys...
. Together, these cause approximately 75% of all adult cases. Certain geographic areas have a high incidence of HIV nephropathy.
Historically, kidney disease has been classified according to the part of the renal anatomy that is involved, to wit:
- VascularVascularVascular in zoology and medicine means "related to blood vessels", which are part of the circulatory system. An organ or tissue that is vascularized is heavily endowed with blood vessels and thus richly supplied with blood....
, includes large vessel disease such as bilateral renal artery stenosisRenal artery stenosisRenal artery stenosis is the narrowing of the renal artery, most often caused by atherosclerosis or fibromuscular dysplasia. This narrowing of the renal artery can impede blood flow to the target kidney...
and small vessel disease such as ischemic nephropathy, hemolytic-uremic syndromeHemolytic-uremic syndromeHemolytic-uremic syndrome , abbreviated HUS, is a disease characterized by hemolytic anemia, acute renal failure and a low platelet count . It predominantly, but not exclusively, affects children. Most cases are preceded by an episode of diarrhea caused by E. coli O157:H7, which is acquired as a...
and vasculitisVasculitisVasculitis refers to a heterogeneous group of disorders that are characterized by inflammatory destruction of blood vessels. Both arteries and veins are affected. Lymphangitis is sometimes considered a type of vasculitis... - Glomerular, comprising a diverse group and subclassified into
- Primary Glomerular disease such as focal segmental glomerulosclerosisFocal segmental glomerulosclerosisFocal segmental glomerulosclerosis is a cause of nephrotic syndrome in children and adolescents, as well as an important cause of kidney failure in adults.It is also known as "focal glomerular sclerosis" or "focal nodular glomerulosclerosis"....
and IgA nephritis - Secondary Glomerular disease such as diabetic nephropathyDiabetic nephropathyDiabetic nephropathy , also known as Kimmelstiel-Wilson syndrome, or nodular diabetic glomerulosclerosis and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and diffuse...
and lupus nephritisLupus nephritisLupus nephritis is an inflammation of the kidney caused by systemic lupus erythematosus , a disease of the immune system. Apart from the kidneys, SLE can also damage the skin, joints, nervous system and virtually any organ or system in the body....
- Primary Glomerular disease such as focal segmental glomerulosclerosis
- Tubulointerstitial including polycystic kidney diseasePolycystic kidney diseaseAutosomal dominant polycystic kidney disease is an inherited systemic disorder that predominantly affects the kidneys, but may affect other organs including the liver, pancreas, brain, and arterial blood vessels...
, drug and toxin-induced chronic tubulointerstitial nephritis and reflux nephropathyReflux nephropathyReflux nephropathy, RN is a term applied when small and scarred kidneys are associated with vesico-ureteric reflux . CPN being the most common cause, there are other causes including analgesic nephropathy and obstructive injury. Scarring is essential in developing RN and occurs almost during the... - Obstructive such as with bilateral kidney stoneKidney stoneA kidney stone, also known as a renal calculus is a solid concretion or crystal aggregation formed in the kidneys from dietary minerals in the urine...
s and diseases of the prostateProstateThe prostate is a compound tubuloalveolar exocrine gland of the male reproductive system in most mammals.... - On rare cases, pin worms infecting the kidney can also cause nephropathy.
Diagnosis
In many CKD patients, previous renal disease or other underlying diseases are already known. A small number present with CKD of unknown cause. In these patients, a cause is occasionally identified retrospectively.It is important to differentiate CKD from acute renal failure
Acute renal failure
Acute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
(ARF) because ARF can be reversible. Abdominal ultrasound
Medical ultrasonography
Diagnostic sonography is an ultrasound-based diagnostic imaging technique used for visualizing subcutaneous body structures including tendons, muscles, joints, vessels and internal organs for possible pathology or lesions...
, in which the size of the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
s is measured, is commonly performed. Kidneys with CKD are usually smaller (< 9 cm) than normal kidneys, with notable exceptions such as in diabetic nephropathy
Diabetic nephropathy
Diabetic nephropathy , also known as Kimmelstiel-Wilson syndrome, or nodular diabetic glomerulosclerosis and intercapillary glomerulonephritis, is a progressive kidney disease caused by angiopathy of capillaries in the kidney glomeruli. It is characterized by nephrotic syndrome and diffuse...
and polycystic kidney disease
Polycystic kidney disease
Autosomal dominant polycystic kidney disease is an inherited systemic disorder that predominantly affects the kidneys, but may affect other organs including the liver, pancreas, brain, and arterial blood vessels...
. Another diagnostic clue that helps differentiate CKD from ARF is a gradual rise in serum creatinine (over several months or years) as opposed to a sudden increase in the serum creatinine (several days to weeks). If these levels are unavailable (because the patient has been well and has had no blood tests), it is occasionally necessary to treat a patient briefly as having ARF until it has been established that the renal impairment is irreversible.
Additional tests may include nuclear medicine
Nuclear medicine
In nuclear medicine procedures, elemental radionuclides are combined with other elements to form chemical compounds, or else combined with existing pharmaceutical compounds, to form radiopharmaceuticals. These radiopharmaceuticals, once administered to the patient, can localize to specific organs...
MAG3 scan to confirm blood flows and establish the differential function between the two kidneys. DMSA
Dimercaptosuccinic acid
Dimercaptosuccinic acid , is the organosulfur compound with the formula HO2CCHCHCO2H. This colorless solid contains two carboxylic acid and two thiol groups, the latter being responsible for its mildly unpleasant odour. It occurs in two diastereomers, meso and the chiral dl forms...
scans are also used in renal imaging; with both MAG3 and DMSA being used chelated
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....
with the radioactive element Technetium-99
Technetium-99
Technetium-99 is an isotope of technetium which decays with a half-life of 211,000 years to stable ruthenium-99, emitting soft beta rays, but no gamma rays....
.
In chronic renal failure treated with standard dialysis, numerous uremic toxins accumulate. These toxins show various cytotoxic activities in the serum, have different molecular weights and some of them are bound to other proteins, primarily to albumin. Such toxic protein bound substances are receiving the attention of scientists who are interested in improving the standard chronic dialysis procedures used today.
Stages
All individuals with a glomerular filtration rate (GFR) <60 mL/min/1.73 m2 for 3 months are classified as having chronic kidney disease, irrespective of the presence or absence of kidney damage. The rationale for including these individuals is that reduction in kidney function to this level or lower represents loss of half or more of the adult level of normal kidney function, which may be associated with a number of complications.All individuals with kidney damage are classified as having chronic kidney disease, irrespective of the level of GFR. The rationale for including individuals with GFR > 60 mL/min/1.73 m2 is that GFR may be sustained at normal or increased levels despite substantial kidney damage and that patients with kidney damage are at increased risk of the two major outcomes of chronic kidney disease: loss of kidney function and development of cardiovascular disease.
The loss of protein in the urine
Proteinuria
Proteinuria means the presence of anexcess of serum proteins in the urine. The protein in the urine often causes the urine to become foamy, although foamy urine may also be caused by bilirubin in the urine , retrograde ejaculation, pneumaturia due to a fistula, or drugs such as pyridium.- Causes...
is regarded as an independent marker for worsening of renal function and cardiovascular disease. Hence, British guidelines append the letter "P" to the stage of chronic kidney disease if there is significant protein loss.
Stage 1
Slightly diminished function; kidney damage with normal or relatively high GFR (≥90 mL/min/1.73 m2). Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies.
Stage 2
Mild reduction in GFR (60–89 mL/min/1.73 m2) with kidney damage. Kidney damage is defined as pathological abnormalities or markers of damage, including abnormalities in blood or urine test or imaging studies.
Stage 3
Moderate reduction in GFR (30–59 mL/min/1.73 m2). British guidelines distinguish between stage 3A (GFR 45–59) and stage 3B (GFR 30–44) for purposes of screening and referral.
Stage 4
Severe reduction in GFR (15–29 mL/min/1.73 m2)
Preparation for renal replacement therapy
Stage 5
Established kidney failure (GFR <15 mL/min/1.73 m2, or permanent renal replacement therapy (RRT)
NDD-CKD vs. ESRD
The term non-dialysis dependent CKDCKD
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, also abbreviated as NDD-CKD, is a designation used to encompass the status of those persons with an established CKD
CKD
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who do not yet require the life-supporting treatments for renal failure
Renal failure
Renal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
known as renal replacement therapy
Renal replacement therapy
Renal replacement therapy is a term used to encompass life-supporting treatments for renal failure.It includes:*hemodialysis,*peritoneal dialysis,*hemofiltration and*renal transplantation.These treatments will not cure chronic kidney disease...
(including maintenance dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
or renal transplantation). The condition of individuals with CKD
CKD
A knock-down kit is a kit containing the parts needed to assemble a product...
, who require either of the 2 types of renal replacement therapy
Renal replacement therapy
Renal replacement therapy is a term used to encompass life-supporting treatments for renal failure.It includes:*hemodialysis,*peritoneal dialysis,*hemofiltration and*renal transplantation.These treatments will not cure chronic kidney disease...
(dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
or transplantation), is referred to as the end-stage renal disease (ESRD). Hence, the start of the ESRD is practically the irreversible
Irreversible
Irreversible may refer to:*Irreversible process, in thermodynamics, a process that is not reversible*Irréversible, a 2002 film*Irréversible , soundtrack to the film Irréversible...
conclusion of the NDD-CKD. Even though the non-dialysis dependent status refers to the status of persons with earlier stages of CKD
CKD
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(stages 1 to 4), patients with advanced stage of CKD
CKD
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(Stage 5), who have not yet started renal replacement therapy
Renal replacement therapy
Renal replacement therapy is a term used to encompass life-supporting treatments for renal failure.It includes:*hemodialysis,*peritoneal dialysis,*hemofiltration and*renal transplantation.These treatments will not cure chronic kidney disease...
are also referred to as NDD-CKD.
Screening and Referral
Early identification of patients with kidney disease is recommended, as measures may be instituted to slow progression and mitigate cardiovascular risk. Among those who should be screened are subjects with hypertension or history of cardiovascular disease, those with diabetes or marked obesity, those aged > 60 years, subjects with indigenous (native American Indian, First Nations) racial origin, those with a history of renal disease in the past, as well as subjects who have relatives who had kidney disease requiring dialysis. Screening should include calculation of estimated GFR/1.73 m2 from the serum creatinine level, and measurement of urine-to-albumin creatinine ratio in a first-morning urine specimen as well as dipstick screen for hematuria. Guidelines for nephrologist referral vary among different countries. Nephrology referral is useful when eGFR/1.73m2 is less than 30 or decreasing by more than 3 mL/min/year, when urine albumin-to-creatinine ratio is more than 300 mg/g, when blood pressure is difficult to control, or when hematuria or other findings suggest either a primarily glomerular disorder or secondary disease amenable to specific treatment. Other benefits of early nephrology referral include proper patient education regarding options for renal replacement therapy as well as pre-emptive transplantation, and timely workup and placement of an arteriovenous fistula in those patients opting for future hemodialysis.Treatment
The goal of therapy is to slow down or halt the progression of CKD to stage 5. Control of blood pressureBlood pressure
Blood pressure is the pressure exerted by circulating blood upon the walls of blood vessels, and is one of the principal vital signs. When used without further specification, "blood pressure" usually refers to the arterial pressure of the systemic circulation. During each heartbeat, BP varies...
and treatment of the original disease, whenever feasible, are the broad principles of management. Generally, angiotensin converting enzyme inhibitors (ACEIs) or angiotensin II receptor antagonists (ARBs) are used, as they have been found to slow the progression of CKD to stage 5. Although the use of ACE inhibitors and ARBs represents the current standard of care for patients with CKD, patients progressively lose kidney function while on these medications, as seen in the IDNT and RENAAL studies, which reported a decrease over time in estimated glomerular filtration rate (an accurate measure of CKD progression, as detailed in the K/DOQI guidelines) in patients treated by these conventional methods.
Currently, several compounds are in development for CKD. These include, but are not limited to, bardoxolone methyl
Bardoxolone methyl
Bardoxolone methyl is an orally-available first-in-class synthetic triterpenoid belonging to the antioxidant inflammation modulator class...
, olmesartan medoxomil, sulodexide
Sulodexide
Sulodexide is a highly purified mixture of glycosaminoglycans composed of low molecular weight heparin and dermatan sulfate .-Pharmacology:...
, and avosentan.
Replacement of erythropoietin
Erythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
and calcitriol
Calcitriol
Calcitriol , also called 1,25-dihydroxycholecalciferol or 1,25-dihydroxyvitamin D3, is the hormonally active form of vitamin D with three hydroxyl groups...
, two hormones processed by the kidney, is often necessary in patients with advanced CKD. Phosphate binders
Phosphate binders
Phosphate binders are a group of medications used to reduce the absorption of phosphate and taken with meals and snacks. They are typically used in patients with chronic renal failure as they cannot get rid of the phosphates that get into their blood Phosphate binders are a group of medications...
are also used to control the serum phosphate
Phosphate
A phosphate, an inorganic chemical, is a salt of phosphoric acid. In organic chemistry, a phosphate, or organophosphate, is an ester of phosphoric acid. Organic phosphates are important in biochemistry and biogeochemistry or ecology. Inorganic phosphates are mined to obtain phosphorus for use in...
levels, which are usually elevated in advanced chronic kidney disease.
When one reaches stage 5 CKD, renal replacement therapy
Renal replacement therapy
Renal replacement therapy is a term used to encompass life-supporting treatments for renal failure.It includes:*hemodialysis,*peritoneal dialysis,*hemofiltration and*renal transplantation.These treatments will not cure chronic kidney disease...
is required, in the form of either dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
or a transplant.
The normalization of hemoglobin has not been found to be of any benefit.
People with CKD are at a markedly increased risk of cardiovascular disease, and often have other risk factors for heart disease, such as hyperlipidemia
Hyperlipidemia
Hyperlipidemia, hyperlipoproteinemia, or hyperlipidaemia is the condition of abnormally elevated levels of any or all lipids and/or lipoproteins in the blood...
. The most common cause of death in people with CKD is therefore cardiovascular disease rather than renal failure. Aggressive treatment of hyperlipidemia is warranted.
Prognosis
The prognosis of patients with chronic kidney disease is guarded as epidemiological dataEpidemiology
Epidemiology is the study of health-event, health-characteristic, or health-determinant patterns in a population. It is the cornerstone method of public health research, and helps inform policy decisions and evidence-based medicine by identifying risk factors for disease and targets for preventive...
has shown that all cause mortality
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....
(the overall death rate) increases as kidney function decreases. The leading cause of death in patients with chronic kidney disease is cardiovascular disease, regardless of whether there is progression to stage 5.
While renal replacement therapies
Renal replacement therapy
Renal replacement therapy is a term used to encompass life-supporting treatments for renal failure.It includes:*hemodialysis,*peritoneal dialysis,*hemofiltration and*renal transplantation.These treatments will not cure chronic kidney disease...
can maintain patients indefinitely and prolong life, the quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
is severely affected. Renal transplantation increases the survival of patients with stage 5 CKD significantly when compared to other therapeutic options; however, it is associated with an increased short-term mortality (due to complications of the surgery). Transplantation aside, high intensity home hemodialysis
Home hemodialysis
Home hemodialysis , is the provision of hemodialysis in the home of people with stage 5 chronic kidney disease. In the US home hemodialysis was the most common method of renal replacement therapy in the early 1970s before the introduction of the Federal ESRD program under Medicare...
appears to be associated with improved survival and a greater quality of life
Quality of life
The term quality of life is used to evaluate the general well-being of individuals and societies. The term is used in a wide range of contexts, including the fields of international development, healthcare, and politics. Quality of life should not be confused with the concept of standard of...
, when compared to the conventional three times a week hemodialysis
Hemodialysis
In medicine, hemodialysis is a method for removing waste products such as creatinine and urea, as well as free water from the blood when the kidneys are in renal failure. Hemodialysis is one of three renal replacement therapies .Hemodialysis can be an outpatient or inpatient therapy...
and peritoneal dialysis
Peritoneal dialysis
Peritoneal dialysis is a treatment for patients with severe chronic kidney disease. The process uses the patient's peritoneum in the abdomen as a membrane across which fluids and dissolved substances are exchanged from the blood...
.
Epidemiology
In Canada 1.9 to 2.3 million people have chronic kidney disease.In the US, the Centers for Disease Control and Prevention
Centers for Disease Control and Prevention
The Centers for Disease Control and Prevention are a United States federal agency under the Department of Health and Human Services headquartered in Druid Hills, unincorporated DeKalb County, Georgia, in Greater Atlanta...
found that CKD affected an estimated 16.8% of adults aged 20 years and older, during 1999 to 2004.
UK estimates suggest that 8.8% of the population of Great Britain and Northern Ireland have symptomatic CKD.
Chronic kidney disease (CKD) is a major concern in African Americans, mostly due to increased prevalence of hypertension. As an example, 37% of end-stage renal disease cases in African Americans can be attributed to high blood pressure, compared with 19% among caucasians. Treatment efficacy also differs between racial groups. Administration of anti-hypertensive drugs generally halts disease progression in white populations, but has little effect in slowing renal disease among blacks, and additional treatment such as bicarbonate therapy is often required. While lower socioeconomic status contributes to prevalence of CKD, there are still significant differences in CKD prevalence between African Americans and whites when controlling for environmental factors.
Studies have shown that there is a true association between history of chronic renal failure in first or second-degree relatives, and risk of disease. In addition, African Americans may have higher serum levels of human leukocyte antigens (HLA). High HLA concentrations can contribute to increased systemic inflammation, which indirectly may lead to heightened susceptibility for developing kidney disease. Lack of nocturnal reduction in blood pressure among groups of African Americans is also offered as an explanation, which lends further credence to a genetic etiology of CKD racial disparities.
Organizations
In the USA, the National Kidney FoundationNational Kidney Foundation
The National Kidney Foundation, Inc. is a major voluntary health organization in the United States, headquartered in New York City...
is a national organization representing patients and professionals who treat kidney diseases. The American Kidney Fund
American Kidney Fund
The American Kidney Fund is a non-profit organization founded in 1971.In 2010 the American Kidney Fund provided more than $200 million in treatment-related financial assistance to more than 101,000 dialysis patients nationwide....
(AKF) is a national non-profit organization providing treatment-related financial assistance to 1 out of every 5 dialysis patients each year. The Renal Support Network
Renal Support Network
The Renal Support Network is an American nonprofit, kidney patient-focused, kidney patient-run organization that works to benefit individuals affected by chronic kidney disease...
(RSN) is a nonprofit, patient-focused, patient-run organization that provides non-medical services to those affected by CKD. The American Association of Kidney Patients (AAKP) is a non-profit, patient-centric group focused on improving the health and well-being of CKD and dialysis
Dialysis
In medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
patients. The Renal Physicians Association
Renal Physicians Association
The Renal Physicians Association is an association representing nephrology professionals in the United States. RPA was founded in 1973 and headquartered in Rockville, Maryland...
(RPA) is an association representing nephrology
Nephrology
Nephrology is a branch of internal medicine and pediatrics dealing with the study of the function and diseases of the kidney.-Scope of the specialty:...
professionals.
In the United Kingdom, the UK National Kidney Federation
UK National Kidney Federation
The UK National Kidney Federation, founded 1979, is the only national kidney charity run by patients with kidney problems or their carers, for kidney patients.The controlling council consists of the patient Associations of hospital renal units...
represents patients, and the Renal Association
Renal Association
The Renal Association is a British professional organisation of nephrologists . It was founded in 1950 by Arthur Arnold Osman after the example of the French Societé de Pathologie Renale. The current president is Professor Peter Mathieson...
represents renal physicians and works closely with the National Service Framework
National Service Framework
National Service Frameworks are policies set by the National Health Service in the United Kingdom to define standards of care for major medical issues such as cancer, coronary heart disease, mental health and diabetes...
for kidney disease.
Kidney Health Australia serves that country.
The International Society of Nephrology
International Society of Nephrology
The International Society of Nephrology is an international body representing specialists in nephrology . Its headquarters are located in Brussels, Belgium....
is an international body representing specialists in kidney diseases.
See also
- Acute renal failureAcute renal failureAcute kidney injury , previously called acute renal failure , is a rapid loss of kidney function. Its causes are numerous and include low blood volume from any cause, exposure to substances harmful to the kidney, and obstruction of the urinary tract...
- DialysisDialysisIn medicine, dialysis is a process for removing waste and excess water from the blood, and is primarily used to provide an artificial replacement for lost kidney function in people with renal failure...
- Hepatorenal syndromeHepatorenal syndromeHepatorenal syndrome is a life-threatening medical condition that consists of rapid deterioration in kidney function in individuals with cirrhosis or fulminant liver failure...
- Renal failureRenal failureRenal failure or kidney failure describes a medical condition in which the kidneys fail to adequately filter toxins and waste products from the blood...
- Artificial kidneyArtificial kidneyArtificial kidney is often a synonym for hemodialysis, but may also, more generally, refer to renal replacement therapies that are in use and/or in development...
- NephropathyNephropathyNephropathy refers to damage to or disease of the kidney. An older term for this is nephrosis.-Causes:Causes of nephropathy include administration of analgesics, xanthine oxidase deficiency, and long-term exposure to lead or its salts...